In vitro Evaluation of Solute Removal Characteristics in Intermittent Infusion Hemodiafiltration.

BACKGROUND: In a typical hemodialysis (HD) session, excessive water removal sometimes induces peripheral circulatory failure and a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF), a new modality of dialysis therapy, has been developed to improve peripheral circulation by repeated intermittent infusion of dialysate during an HD session. In a typical I-HDF session, we infuse a volume of 200 mL of ultrapure dialysate by backfiltration at 150 mL/min every 30 min. The same volume is alternately removed from the patient's blood by filtration at a constant rate after each infusion. However, solute removal characteristics in I-HDF have not been clarified previously. We therefore conducted an in vitro study to investigate the characteristics of solute removal and the factors affecting such removal. SUMMARY: We used human plasma to evaluate the effects of filtration (QF)/infusion (QI) flow rates on solute clearance (CL) and to estimate the time-averaged solute CL (TACL) values. The CL values for all solutes decreased with increasing QI. For small molecules such as urea, the CL values predominantly decreased with increasing QI because of decreasing diffusive transport. For medium and large solutes such as ß2 microglobulin or larger, CL values predominantly increased with increasing QF because of increasing convective transport. However, the effects of these changes on TACL values were small compared with the CL value in a typical HD session because of the alternate filtration and infusion in I-HDF. Key Messages: Solute removal characteristics in I-HDF do not differ significantly from those in conventional HD treatment.

[Roles of and Team Medical Care Involving Clinical Engineers in Blood Purification Therapy].

Progress in medical care strongly depends on the development of pharmaceutical and medical technologies. Multi-disciplinary care by a medical team is required for the diversity of medical care. "Clinical engineering technician (CET) " is one of the national medical licenses in Japan. Many CETs are engaged in blood purification therapies. Team medical care, involving medical doctors, nurses, CETs, etc., in the hemodialysis field is useful for the early detection of complications in dialysis patients and provision of appropriate treatments. In some medical facilities, for example, progressive approaches such as appropriate nutritional guidance by a dietitian or exercise therapy by a physical therapist are practiced in advance. Clinical laboratory technologists (CLTs), furthermore, play an important role in team medical care for dial- ysis therapy. They can use ultrasonic equipment for vascular access management. Based on the results of the ABI and SPP measurements by CLTs, medical doctors can diagnose PAD in dialysis patients. [Review].

Performance evaluation of developed polysulfone membrane hemodiafilters, ABH-F and ABH-P, in post- and pre-dilution hemodiafiltration.

ABH-F and ABH-P have been developed for hemodiafiltration (HDF) therapy. In this study, we evaluated the solute removal characteristics of the hemodiafilters in a bovine blood in vitro study. The hemodiafilters were examined for 120 min at various filtration flow rates (Q F) (31.2-250 mL/min) under a constant blood flow rate of 250 mL/min and constant dialysate flow rates of 500/250 mL/min in pre-dilution HDF (pre-HDF) and post-dilution HDF (post-HDF). Creatinine clearance in pre-HDF was approximately 85% of that in post-HDF because it was removed by molecular diffusion dominantly. The initial clearances of ß2-microglobulin and α1-microglobulin increased with Q F and these values slightly and steeply decreased with time due to membrane fouling. Under a same Q F of 62.5 mL/min, higher clearance values in post-HDF were obtained compared with those in pre-HDF. All clearance values of ABH-P were higher than those of ABH-F under the same Q F. It seems that the ABH-P has a larger pore size of membrane than that in ABH-F. The creatinine and α1-microglobulin clearance values were obtained as highest at post-Q F62.5, the ß2-microglobulin clearance values and transmembrane pressure were obtained as highest at pre-Q F250. Large solute clearances such as α1-microglobulin and albumin decreased with time in all HDF experiments. Time decay of large solute clearance values was observed in the HDF modality that had a higher clearance of the solute at 5 min later after the start of experiment.

Effect of blood flow rate on internal filtration in a high-flux dialyzer with polysulfone membrane.

Internal filtration/backfiltration (IF/BF) of a dialyzer depends on several parameters. This study evaluated the effect of the blood flow rate (Q (B)) on the internal filtration flow rate (Q (IF)) measured using Doppler ultrasonography for a high-flux dialyzer with a polysulfone membrane, APS-15E. In an in vitro study, bovine blood was circulated through the dialyzer, at a Q (B) of 100-350 mL/min. The clearances (CL) of creatinine, ß(2)-microglobulin, and α(1)-microglobulin were then investigated. Q (IF) increased with the Q (B) value. A good correlation was obtained between Q (IF) and the pressure difference between the pressures at the inlet of the blood compartment and the pressure at the outlet of the dialysate compartment. The creatinine CL values strongly depended on Q (B) because molecular diffusion was dominant. The ß(2)-microglobulin CL also depended on Q (B), because its removal rate seemed to be affected by both diffusive and convective transport caused by the IF/BF. An extremely low CL value was obtained for α(1)-microglobulin because of its low diffusivity and membrane fouling induced by proteins plugging the membrane. In conclusion, the IF/BF in the dialyzer strongly depends on Q (B). Furthermore, the dependence of the solute clearance on Q (B) decreased with increasing molecular size of the solute because of the decrease in diffusivity through the membrane.

Clinical results and pharmacokinetics of sorafenib in chronic hemodialysis patients with metastatic renal cell carcinoma in a single center.

OBJECTIVE: We investigated the safety and feasibility of sorafenib in patients with end-stage renal disease undergoing hemodialysis by examining the influence of pharmacokinetic parameters to their benefit and also the occurrence of drug-related adverse events of sorafenib. METHODS: Ten patients with metastatic renal cell carcinoma undergoing hemodialysis received sorafenib. Initial dose was 200 mg once daily, and the dose was increased up to the maintenance dose of 200 mg twice daily. The pharmacokinetic study was performed after a steady state was reached with 200 mg twice daily in six patients. RESULTS: Complete response occurred in one patient, partial response in three, stable disease in four and progressive disease in two. Median progression-free survival was 6.3 months. Serious adverse events were found in nine patients, including a Grade 5 subarachnoid hemorrhage and a Grade 4 cerebellar hemorrhage. In the pharmacokinetic study, the geometric mean of maximum concentration and area under the curve from 0 to 10 h of plasma concentration were similar on the day of hemodialysis and the day off hemodialysis. These data were lower than those from Japanese people with healthy kidneys and normal kidney function. There was no association between objective response or the occurrence of serious adverse events and pharmacokinetic parameters. CONCLUSIONS: Treatment with sorafenib of patients with metastatic renal cell carcinoma undergoing hemodialysis appears to be feasible, but we express some concern about the higher incidence of serious adverse events even with the reduced dose. However, clinical efficacy was not compromised.

Validity of internal filtration-enhanced hemodialysis as a new hemodiafiltration therapy.

In order to improve solute removal efficiency, several types of dialyzers with enhanced internal filtration (IF) were introduced for clinical applications. In these dialyzers, enhanced IF increased convective transport of the solute in addition to diffusive transport. Internal filtration-enhanced hemodialysis (IFEHD) defined as hemodialysis therapy using the enhanced IF dialyzer seems to be more convenient in comparison with conventional hemodiafiltration therapies because of no additional equipments such as a roller pump. In this paper, the validity of IFEHD was examined during several types of experimental studies. As a result, the experimental study with several types of enhanced IF dialyzers indicated values of relative solute clearance in an aqueous solution that were higher than unity compared to the conventional dialyzer. The K values obtained for myoglobin as a larger molecule were more than twice as high. The value of IF flow rate (Q(IF)) was evaluated by pulsed Doppler ultrasonography. The blood flow velocity at a cross-sectional plane of the dialyzer was directly measured along the dialyzer during a bovine in vitro study using a newly developed probe slider. Doppler ultrasonography is a useful method as a bedside monitoring of the Q(IF) value in a dialyzer because it is noninvasive for the patient. Time course of the Q(IF) value was examined for 6 h during a bovine in vitro study. The Q(IF) decreased within 45 min after the start of the experiment and reached constant values after that. Although creatinine and beta(2)-microglobulin K values remained constant with time during the experiment, alpha(1)-microglobulin K values gradually and albumin K value steeply decreased with time. This is because these solutes transfer through the membrane strongly affected by fouling. The validity of IFEHD was clarified during the experimental studies. Development of a dialyzer with enhanced IF, however, should take account of the patient's safety. Contaminations such as endotoxin invasion from the dialysate to the patient should be avoided.